The broad-based pathogenesis study described here accomplishes all of the AREA program objectives (1) supporting meritorious research by qualified scientists, (2) exposing undergraduates to biomedical research and thus encouraging their pursuit of graduate studies in the health sciences, and (3) strengthening the research environments in non-research intensive schools. The experimental model, Bordetella avium, causes a highly contagious respiratory disease in its avian hosts that has striking similarity to whooping cough in children, caused by B. pertussis. We have the advantage of observing B. avium in its natural host, in contrast to the research of other bordetellae, which lack acceptable animal models. Using genetic, biochemical, and bioinformatics tools, we have identified a number of genes implicated in disease causation, and have begun construction of several deletion mutants. The chromosomal sequence of our wild type laboratory strain was obtained;the analysis revealed major differences in genes expected to encode cell surface structures that likely mediate the species specificity of this organism for avian tissues. We have developed an explant culture system for ciliated cells from embryonic turkey trachea and purified cilia from adult turkey trachea. Finally, we have done preliminary comparative genome hybridization studies to determine the overall genetic relatedness among isolates. In the proposed study, we will collect a number of new B. avium isolates from wild birds and commercial turkeys, as well as creating deletion mutants of specific genes predicted to be important in disease causation. We will use the genomic information as well as a panel of in vivo and in vitro assays to determine the serologic and genetic relationship and relative virulence of each strain. This will give us information that is essential in order to create a non-virulent, colonizing strain that can be used as a vaccine. Over the three-year funding period, the project will expose 25-30 students to an excellent model of research and give them an opportunity to make unique contributions to the study of an important pathogen. A broad- based approach provides students with numerous opportunities to creatively explore scientific questions while learning the fundamentals of biomedical research. This ongoing collaborative study, now expanded to include both James Madison University and Drew University, is a catalyst for increasing faculty and student interest in research and enhancing the quality of the research environment in these two primarily undergraduate schools. This study proposes to learn more about disease causation by Bordetella avium, a pathogen of birds that causes economic loss in the poultry industry. The work has potential for vaccines effectively eradicating the disease. The similarity of this organism to a human pathogen also holds promise for understanding the human disease, whooping cough.